Block egg suicide to guard fertility after cancer therapy

A new way of preventing infertility stops eggs from destroying themselves. Blocking the proteins that cause an egg to self-destruct when damaged could one day help women maintain fertility following cancer therapy, and potentially stave off the menopause.

Human eggs are sensitive cells. Soon after birth, a significant proportion of the store of underdeveloped eggs that a woman is born with are destroyed. Egg cells continue to die off with age until menopause.

Cancer treatments that involve radiation can also wipe out egg cells by damaging their DNA, which causes them to self-destruct.

Researchers have already identified around seven “killer proteins” that initiate this cell death. Clare Scott at the Walter and Eliza Hall Institute of Medical Research in Victoria, Australia, and colleagues, have found that two of these proteins – PUMA and NOXA – seem to be particularly important in killing egg cells exposed to DNA damage, which can result from normal ageing or radiation. Self-destruction normally works in the cells’ favour since damaged cells can become cancerous.

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In an attempt to protect egg cells from their killer proteins, Scott’s team exposed healthy mice as well as those bred to lack one or both of the proteins, to low doses of radiation.

Five days after exposure, mice with a full set of proteins had lost all their egg cells. Those lacking PUMA, however, retained 15 per cent of their original store of eggs. Mice lacking both PUMA and NOXA appeared especially hardy, retaining more than half of their eggs.

Curiously, when the researchers ramped up the radiation to a level that was half of what would kill the animals, the mice lacking both proteins retained 94 per cent of their egg store.

What’s more, the rescued eggs appeared healthy. “The really exciting thing is that if you can prevent PUMA and NOXA from killing them, the eggs have a chance to repair their own DNA,” says Scott. “The DNA is remarkably robust.” The mice went on to have pups, which were healthy and fertile, she adds.

Scott hopes that a drug developed to target PUMA in egg cells could help women maintain their fertility during cancer treatments. There’s no need to target both proteins, she says, since saving 15 per cent of the eggs is enough to keep a woman fertile.

Such a drug might also stave off the menopause and its associated risks of osteoporosis and heart problems, says Scott. “The best way to have normal levels of oestrogen and progesterone are for the body to make them, rather than using hormone replacement therapy,” she says. “The way to do this is to keep egg cells alive.”